Study of placental formation and functional differentiation by tissue specific stem cell transplantation

胎盘在子宫内胎儿的生长发育中起着至关重要的作用。任何对胎盘发育的侮辱，如免疫反应异常或母亲营养不良，都可能导致胎盘生长不良和胎盘功能不全。在目前的研究中，我们通过将母亲骨髓来源的单个核细胞移植到生长中的胎盘来评估这些细胞在胎盘发育中的作用。从GFP转基因小鼠获得的骨髓细胞被注射到生长中的胎盘中，并在分娩前被观察到保留在胎盘组织中。此外，在GFP转基因母鼠子宫内生长的非GFP仔鼠的胎盘中观察到GFP阳性的母体单个核细胞，提示母体单个核细胞可能在胎盘的形成中起一定作用。在本研究中，我们还阐明了糖皮质激素失活酶11β-羟基类固醇脱氢酶2(11βHSD2)的参与。11βHSD2在小鼠胎盘绒毛上皮细胞有表达。妊娠期限制饮食可增加胎盘组织中β-HSD2的表达。因此，这意味着胎儿受到保护，不会因食物限制应激而增加母体循环中糖皮质激素的暴露。此外，在限食期间饲喂高蛋白饲料，胎盘11βHSD2的表达进一步增加，同时改善了胎儿的生长。这些发现可能会给我们提供线索，以开发新的策略，以获得良好的胎儿结局。

The placenta plays an essential role in the growth of fetus in the uterus. Any insult in placental development, such as abnormal immune reaction or maternal malnutrition, can result in poor placental growth and placental insufficiency. In the present study, we evaluated an involvement of maternal bone-marrow derived mononuclear cells in the development of the placenta by transplanting these cells in growing placenta. Bone-marrow cells obtained from GFP transgenic mice were injected in the growing placenta and was observed to be retained in the placental tissue just prior to delivery. Moreover, GFP positive maternal mononuclear cells were observed in the placenta of non-GFP pups growing in the uterus of GFP transgenic dams, thus indicating that maternal mononuclear cells may contribute somehow to the formation of the placenta. In the present study, we also elucidated an involvement of glucocorticoid inactivating enzyme, 11 beta-hydroxysteroid dehydrogenase type 2(11βHSD2). 11βHSD2 was expressed in chorionic epithelium of the mouse placenta. 11βHSD2 expression in the placenta was increased by maternal food restriction during pregnancy. Therefore, it is implicated that fetus is protected from exposure to glucocorticoid in maternal circulation increased by food restriction stress. In addition, placental 11βHSD2 expression was further increased by feeding high protein diet during food restriction, together with improved fetal growth. These findings may give us a clue to develop a new strategy to have a good fetal outcome.